High purity filtration of aqueous media, such as in the fields of biotechnology, chemistry, electronics, pharmaceuticals, and the food and beverage industries requires the use of sophisticated filter modules that are not only capable of a high degree of separation, but that will tend to prevent contamination of the environment, of the medium to be filtered, and of the resulting filtrate. This is designed to prevent unwanted, often dangerous organisms, such as bacteria or viruses, as well as environmental contaminants, such as dust, dirt, and the like from entering into the process stream and end product. Similarly, filter capsules help to prevent contamination of a highly validated clean room due to exposure from the contents of the process stream. To ensure sterility, it would be desirable to have a completely sealed system. However this is not always possible with the processes that take place in production.
To ensure sterility of the filtrate, filter modules must maintain their integrity throughout the filtration process. Accordingly, integrity testing of sterilizing filters is a fundamental requirement of critical process filtration applications in the pharmaceutical industry. General guidelines require integrity testing of filter modules after filtration, and recommend integrity testing of filter modules prior to use. Typically this testing is initially performed after sterilization to ensure that the filter is not damaged; accordingly, care must be taken to ensure that sterility of the filter, and thus the filtrate, is not compromised. Post-processing, the filter integrity test may be performed again either in situ or separated from the assembly and tested in a separate room to determine whether the filter was compromised during use. This information can be used to alert operators to a potential problem immediately after processing, and to quickly take corrective action. Further, FDA guidelines require that integrity testing documentation be included with batch product records.
There are a variety of methods of integrity testing, including the diffusion test and the pressure hold test. The diffusion test measures the rate of gas transfer through a filter to be tested. At differential gas pressures below the bubble point, gas molecules migrate through water-filled pores of a wetted membrane following Fick's Law of Diffusion. The gas diffusional flow rate for a filter is proportional to the differential pressure and the total surface area of the filter. At a pressure approximately 80% of the minimum bubble point, the gas which diffuses through the filter membrane can be measured to determine a filter's integrity. A diffusional flow reading exceeding a value stated by the manufacturer indicates a variety of problems, including an incorrect temperature, wrong pore size, incompletely wetted membrane, non-integral membrane or seal, or inadequate stabilization time. The pressure hold test, also known as the pressure decay or pressure drop test, is a variation of the diffusion test. In this test, a highly accurate gauge is used to monitor upstream pressure changes due to gas diffusion through the filter. Because there is no need to measure gas flow downstream of the filter, any risk to downstream sterility is eliminated.
Typically, integrity testing is performed with specialized integrity testing hardware. Examples include the Integritest® 4 Series Automated Filter Integrity Test Instrument (commercially available from EMD Millipore Corporation) and the Sartocheck® line of filter integrity testing systems (commercially available from Sartorius Corporation). To perform integrity testing of a filter module installed in an assembly, an end user would attach the integrity testing hardware to a secondary aseptic connection located upstream of the filter capsule. To ensure that no contaminants are introduced, the secondary aseptic connection may comprise a Lynx ST Valve (commercially available from EMD Millipore Corporation) and an aseptic phobic filter between the capsule filter and the integrity testing equipment. Using clamps or other means, the end user isolates the desired integrity testing flow path from other components of the assembly and activates the integrity testing equipment, which performs the integrity test and provides the result.
However, integrity testing is sensitive to a variety of factors related to the composition and complexity of an assembly. A typical flow path for integrity testing on an assembly may include various tubing, flex points, T-connections, gaskets, and other components between the integrity test hardware and a filter capsule. Integrity testing may stress these components, leading to false integrity test failures that are a result of loose connections or compression. Thus, it may not be clear whether the integrity test is testing the filter or the isolated flow path. Further, including new connections to support integrity testing hardware presents new failure points and increases the complexity of the system. Moreover, attaching integrity testing hardware to components downstream of the filter increases the likelihood of contamination.
In light of the above, a need exists for an improved device, system, and method for performing integrity testing of filter assemblies.